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首页> 外文期刊>Biochemistry >Enzymatic Mechanism of Low-Activity Mouse Alcohol Dehydrogenase 2
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Enzymatic Mechanism of Low-Activity Mouse Alcohol Dehydrogenase 2

机译：低活性小鼠醇脱氢酶2的酶促机制2

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摘要

ADH2 is a member of one of the six classes of mammalian alcohol dehydrogenases,which catalyze the reversible oxidation of alcohols using NAD~+ as a cofactor.Within the ADH2 class,the rodent enzymes form a subgroup that exhibits low catalytic activity with all substrates that were examined,as compared to other groups,such as human ADH2.The low activity can be ascribed to the rigid nature of the proline residue at position 47 as the activity can be increased by approx100-fold by substituting Pro47 with either His (as found in human ADH2),Ala,or Gin.Mouse ADH2 follows an ordered bi-bi mechanism,and hydride transfer is rate-limiting for oxidation of benzyl alcohols catalyzed by the mutated and wild-type enzymes.Structural studies suggest that the mouse enzyme with His47 has a more closed active site,as compared to the enzyme with Pro47,and hydride transfer can be more efficient.Oxidation of benzyl alcohol catalyzed by all forms of the enzyme is strongly pH dependent,with pK values in the range of 8.1-9.3 for turnover numbers and catalytic efficiency.These pK values probably correspond to the ionization of the zinc-bound water or alcohol.The pK values are not lowered by the Pro47 to His substitution,suggesting that His47 does not act as a catalytic base in the deprotonation of the zinc ligand.
机译：ADH2是六种哺乳动物醇脱氢酶之一的成员，其使用NAD〜+作为辅因子催化醇的可逆氧化。在ADH2类中，啮齿动物酶形成具有低催化活性的亚组，其中所有基材都具有低催化活性的亚组被检查，与其他群体相比，如人ADH2。低活性可以归因于47位的脯氨酸残基的刚性性质，因为可以通过用他的Pro47取代Pro47（如发现在人ADH2）中，ALA或GIN.MOUSE ADH2遵循有序的BI-BI机理，氢化物转移是通过突变和野生型酶催化催化的苄醇的氧化率限制。结构研究表明小鼠酶HIS47具有更封闭的活性位点，与PRO47的酶相比，氢化物转移可以更有效。通过所有形式的酶催化的苄醇氧化是强烈的pH依赖性的，在r中具有PK值8.1-9.3的Ange为营业额数和催化效率。这些PK值可能对应于锌粉水或酒精的电离。PK值由PRO47的替代没有降低，这表明HIS47并不充当锌配体的去质子化催化基础。

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  • 来源
    《Biochemistry》 |2004年第5期|共6页
  • 作者

    Patrik Stromberg; Stefan Svensson; Kristine B.Berst; Bryce V.Plapp; Jan-Olov Hoog;

  • 作者单位

    Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden and Department of Biochemistry The University of Iowa Iowa City Iowa 52242;

    Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden and Department of Biochemistry The University of Iowa Iowa City Iowa 52242;

    Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden and Department of Biochemistry The University of Iowa Iowa City Iowa 52242;

    Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden and Department of Biochemistry The University of Iowa Iowa City Iowa 52242;

    Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden and Department of Biochemistry The University of Iowa Iowa City Iowa 52242;

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  • 正文语种 eng
  • 中图分类 生物化学;
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